A PHASE III TRIAL TO EVALUATE THE EFFICACY OF THE ADDITION OF INOTUZUMAB OZOGAMICIN (A CONJUGATED ANTI-CD22MONOCLONAL ANTIBODY) TO FRONTLINE THERAPY IN YOUNG ADULTS (AGES 18-39 YEARS) WITH NEWLY DIAGNOSED PRECURSOR B-CELL ALL

This phase III trial studies the side effects of inotuzumab ozogamicin and how well it
works when given with frontline chemotherapy in treating patients with newly diagnosed B
acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called
inotuzumab, linked to a chemotherapy drug called ozogamicin. Inotuzumab is a form of
targeted therapy because it attaches to specific molecules (receptors) on the surface of
cancer cells, known as CD22 receptors, and delivers ozogamicin to kill them. Chemotherapy
drugs, such as [intervention], work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving inotuzumab ozogamicin with chemotherapy may work better in treating
young adults with B acute lymphoblastic leukemia.

Inclusion Criteria:

REGISTRATION ELIGIBILITY CRITERIA (STEP 1)

- Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia
(WHO criteria) are eligible. Patients with Burkitt type ALL are NOT eligible

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Single-dose intrathecal cytarabine is
allowed prior to registration or prior to initiation of systematic therapy for
patient convenience; this is usually done at the time of the diagnostic bone marrow
or venous line placement to avoid a second lumbar puncture; systemic chemotherapy
must begin within 72 hours of this intrathecal therapy

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Age >= 18 years and < 40 years

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group
(ECOG) performance status 0-2

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST),
alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN), unless suspected
leukemic involvement of the liver

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Direct bilirubin =< 3 x upper limit of
normal (ULN), unless suspected leukemic involvement of the liver

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Calculated (calc.) creatinine clearance
>= 50 mL/min by Cockcroft-Gault

- RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) CONFIRMATION OF TOLERABILITY AND PHASE
III ONLY): Completion of remission induction therapy

- RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) CONFIRMATION OF TOLERABILITY AND PHASE
III ONLY):Patients with M2 marrow or better are eligible; patients with M3 or M4
marrow (greater than 25% lymphoblasts) will not be eligible to be randomized

- Rating: M0, M1; Blast Cells (%): 0-5.0

- Rating: M2; Blast Cells (%): 5.1-25.0

- Rating: M3; Blast Cells (%): > 25-50

- Rating: M4; Blast Cells (%): > 50.0

- The term "blast cell" includes any cell that cannot be classified as a more
mature normal element, and includes "leukemic cells," pathologic lymphocytes,
and stem cells

- RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE
III ONLY): Absolute neutrophil count (ANC) >= 750/mm^3

- RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE
III ONLY): Platelet count >= 75,000/mm^3

- RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE
III ONLY): Total bilirubin =< 1.5 x upper limit of normal (ULN), except for patients
with known Gilbert's syndrome

- RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2) (CONFIRMATION OF TOLERABILITY AND PHASE
III ONLY): Aspartate aminotransferase (AST) =< 8 x upper limit of normal (ULN)

EXCLUSION CRITERIA

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients who have BCR-ABL fusion
transcript determined by fluorescence in situ hybridization (FISH) or real
time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not
eligible and should be considered for enrollment on studies that incorporate
imatinib during induction; please note: patients must also be assessed for CD20
positivity and other markers; positivity for CD22 and CD20 is defined as baseline
expression of the CD22 or CD20 antigen in more than 20% of leukemic cells using
local multiparameter flow-cytometric immunophenotyping with the use of CD45
expression as a marker to gate the ALL blast population, according to
recommendations from the European LeukemiaNet

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior therapy for ALL except for
limited treatment (=< 7 days) with corticosteroids or hydroxyurea and a single dose
of intrathecal cytarabine; however, patients who are being treated with chronic
steroids for other reasons (for example, to treat asthma, autoimmune disorders,
lupus, etc.) are eligible

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior therapy for acute leukemia
except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis,
superior vena cava syndrome, or renal failure due to leukemic infiltration of the
kidneys; when indicated, leukapheresis or exchange transfusion is recommended to
reduce the WBC

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because
this study involves agents that have known genotoxic, mutagenic and teratogenic
effects; therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 8 days prior to registration is required

- REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with down syndrome are excluded
from this study due to the likelihood of excessive toxicity resulting; these
patients should be treated in consultation with a pediatric oncologist